Department of Biomedical Engineering, Particulate Fluids Processing Centre, University of Melbourne, Parkville, VIC 3010, Australia; Polymer Science Group, Department of Chemical Engineering, Particulate Fluid Processing Centre, University of Melbourne, Parkville, VIC 3010, Australia.
School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, VIC 3010, Australia.
Biomaterials. 2018 Dec;187:81-92. doi: 10.1016/j.biomaterials.2018.10.002. Epub 2018 Oct 4.
Biomaterials are a powerful platform for directing cellular behaviour. Herein, we employed a biomimetic strategy to synthesize a low-fouling polymer functionalized with nano-scale clusters of ligands that bind both integrin and syndecan-4 receptors, as both receptor types are critical in focal adhesion signalling and mechanotransduction. Our results demonstrate that the presence of both ligand types synergistically increases the adhesion of human umbilical vein endothelial cells (more than a two fold increase after 4 h) and increases the rate of surface endothelialization compared to surfaces functionalized with only one ligand type. Additionally, we observe that the mixed population of ligands regulates endothelial cell migration, likely due to improved focal adhesion formation as observed through confocal microscopy. Furthermore, we illustrate that only endothelial cells cultured on these mixed ligand surfaces exhibit the appropriate morphological changes - elongation and alignment in the direction of flow - when exposed to laminar shear flow, and neither of the individual ligands alone is sufficient. These results illustrate that both receptor types must be engaged for optimum cell-material interactions and are mandatory for appropriate mechanotransduction. The results presented in this manuscript will be critical for the development of next generation biomedical devices and tissue engineering scaffolds.
生物材料是指导细胞行为的强大平台。在此，我们采用仿生策略合成了一种低污染的聚合物，该聚合物功能化有纳米级配体簇，可结合整合素和 syndecan-4 受体，因为这两种受体类型在粘着斑信号转导和机械转导中都很关键。我们的结果表明，两种配体类型的存在协同增加了人脐静脉内皮细胞的黏附（4 小时后增加了两倍以上），并且与仅用一种配体类型功能化的表面相比，增加了表面内皮化的速度。此外，我们观察到混合配体种群调节内皮细胞迁移，这可能是由于通过共聚焦显微镜观察到粘着斑形成得到改善。此外，我们表明，只有在这些混合配体表面上培养的内皮细胞在暴露于层流剪切流时才会表现出适当的形态变化——在流动方向上的伸长和对齐，而单独的任何一种配体都不足。这些结果表明，两种受体类型都必须参与以实现最佳的细胞-材料相互作用，并且对于适当的机械转导是必需的。本文介绍的结果对于下一代生物医学设备和组织工程支架的开发将是至关重要的。
